Evaluation of cellular tumour rejection mechanisms in the peritumoral bladder wall after bacillus Calmette-Guerin treatment

Objective To compare the immunological status of normal and peritumoral bla dder walls, and to characterize immunocompetent cells before and during int ravesical instillations of bacillus Calmette-Guerin (BCG). Patients and methods Twenty-three patients with superficial urothelial blad der carcinoma (stages pTa to pT1, grades 1-3) were treated with six weekly instillations of 150 mg of BCG (Pasteur strain). Biopsies of cystoscopicall y normal bladder wall were taken before, 3 weeks and 3 months after BCG ins tillation. The controls comprised bladder biopsy specimens from 13 brain-de ad ventilated kidney donors. Local infiltrating cell types, i.e. lymphocyte infiltrates (CD4, CD8, CD20, CD3, interleukin-2-receptor-positive, natural killer, gamma delta), macrophages and dendritic cells, adhesion and costim ulatory molecules (ICAM-1 and B7-BB1) and major histocompatibility complex (MHC) class I and class II antigens were assessed using semiquantitative im munohistochemical analysis. Results Before BCG the peritumoral bladder wall had fewer macrophages than control bladder wall. BCG treatment restored normal numbers of macrophages and enhanced T helper lymphocytes, B lymphocytes, natural killer cells, act ivated lymphocytes, dendritic cells, normal MHC class I, adhesion (ICAM-1) and costimulatory (B7-BB1) expression. The enhancement of these immunologic al variables was transient, with a return to baseline 3 months after BCG in stillation. Conclusions These results support the concept that there is a host-immune e scape associated with bladder cancer. BCG therapy may temporarily restore i mpaired tumour rejection mechanisms in the peritumoral bladder wall, sugges ting a need for maintenance therapy after the First course of BCG.